AbstractThe most common long‐term complication of joint arthroplasty is loosening, which is mediated by chronic inflammatory cytokines produced by macrophages stimulated by implant‐derived debris and eventually bacterial components adherent to such debris. In this study, antiinflammatory interleukin‐1 receptor‐associated kinase‐M (IRAK‐M) was studied in macrophages in interface membranesin vivousing immunohistochemical staining and in titanium particle‐stimulated macrophagesin vitrousing reverse transcriptase‐polymerase chain reaction. Results show that the interface membranes of septically and aseptically loosened prosthesis express more IRAK‐M protein than control membranes from osteoarthritic patient and that IRAK‐M mRNA‐levels increase upon particle stimulation. These findings suggest that, the upregulation of IRAK‐M in macrophages is involved in the local immunosuppression around implants, and may contribute to septic and aseptic implant loosening. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.